Efforts to manufacture a H1N1 vaccine revealed a number of production bottlenecks which led to unanticipated delays. In response, the President’s Council of Advisors on Science and Technology (PCAST) was asked to look into how the US government can improve the situation.
Primarily PCAST sought to answer one question: “How can the federal government help to reduce the time required for the nation to supply effective vaccine to its population when the next influenza pandemic occurs?”
A document answering this question has now been sent to President Obama. In the document PCAST details a number of measures the US government should take, including some short-term actions which could have a significant impact without fundamental changes to manufacturing.
Fill and finish
PCAST regards fill and finish as a “major hurdle” in efforts to respond to a pandemic threat. To tackle this “costly and laborious phase of manufacturing”, which is often “a major rate-limiting step”, PCAST recommends undertaking a comprehensive six month review focused on this area.
The review should assess use of existing facilities or the creation of new plants which could be used in the event of a pandemic. However, PCAST acknowledges that costs for additional facilities “will not be readily adsorbed by the manufacturers”.
An alternative is the adoption of facilities and equipment that can process different vaccines at different times of year. Widespread use would require guidance from regulators to avoid safety violations and production delays.
PCAST also suggests machinery could be improved. To drive innovation in this area the review recommends government incentives are considered, especially if the resulting technology would have applications beyond pandemic response.
Greater use of multi-dose vials is another suggestion. This could save several weeks but also increases the risk of contamination or failure to change needles between doses. Furthermore, multi-dose vials generally require greater use of preservatives.
Other short-term measures
Improving potency assays “should be a high-priority effort” driven by in-house work at the US Food and Drug Administration (FDA) and contracts to firms. Adoption of new methods, such as isotope dilution mass spectrometry, could make vaccines available four to eight weeks sooner.
Changes to sterility testing could also cut pandemic response times. Incubating vaccine material in conventional growth media and waiting for bacterial or fungal growth takes up to two weeks. This could be halved by adopting new methods.
PCAST recommends that alternatives such as PCR and shotgun DNA sequencing are performed in parallel with the current standard to assess sensitivity and validity. This should be supported by FDA guidance on development and implementation.
Development of influenza vaccine seed strains is also suggested. By developing and disseminating a panel of viral backbones PCAST believes vaccine production could be accelerated.
in-PharmaTechnologist will look at the long-term recommendations in a future article.